Association between chronic obstructive pulmonary disease and cardiovascular disease in adults aged 40 years and above: data from NHANES 2013-2018.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD) are two major age-related diseases prevalent in the elderly. However, it is unclear whether there is a higher prevalence of one or more CVDs in COPD patients compared to those without COPD, and the magnitude of this increased prevalence. METHODS: This population-based cross-sectional study was conducted using data from the National Health and Nutrition Examination Survey (NHANES) 2013-2018 among American adults aged 40 years and above. Multivariable logistic regression models (including unadjusted model, minimally adjusted model, and fully adjusted model) were conducted to investigate the association between COPD and the prevalence of one or more CVDs, including coronary heart disease, heart failure, angina pectoris, heart attack, diabetes, and stroke. RESULTS: This study included 11,425 participants, consisting of 661 participants with COPD and 10,764 participants without COPD. COPD patients had a significantly higher prevalence of CVD than those without COPD (59.6% vs. 28.4%). After adjusting for covariates, COPD was significantly associated with the prevalence of one CVD (OR = 2.2, 95% CI = 1.6-3.0, p < 0.001), two or more CVDs (OR = 3.3, 95% CI = 2.2-5.0, p < 0.001), and three or more CVDs (OR = 4.3, 95% CI = 2.9-6.5, p < 0.001). CONCLUSIONS: Patients with COPD have a higher prevalence of one or more CVDs compared with those without COPD. Our findings highlight the importance of CVD prevention and management in patients with COPD.

Comprehensive analysis of epigenomics and transcriptome data to identify potential target genes associated with obesity.

DNA methylation is closely related to the occurrence and development of many diseases, but its role in obesity is still unclear. This study aimed to find the potential differentially methylated genes associated with obesity occurrence and development. By combining methylation and transcriptome analysis, we identified the key genes in adipose tissue affecting the occurrence and development of obesity and revealed the possible molecular mechanisms involved in obesity pathogenesis. We first screened 14 methylation-related differential genes and verified their expression in adipose tissue by quantitative polymerase chain reaction (qPCR). Seven genes with the same expression pattern were identified as key genes, namely, CCRL2, GPT, LGALS12, PC, SLC27A2, SLC4A4, and TTC36. Then, the immune microenvironment of adipose tissue was quantified by CIBERSORT, and we found that the content of M0 macrophages and T follicular helper cells in adipose tissue was significantly increased and decreased, respectively, in the obese group. Furthermore, the relationship between key genes and the immune microenvironment was analyzed. Additionally, the metabolic pathway activity of each sample was calculated based on the ssGSEA algorithm, and the key gene-metabolic network was constructed. Moreover, we performed a CMAP analysis based on the differential genes in adipose tissue to screen out drugs potentially effective in obesity treatment. In conclusion, we identified seven methylation-related key genes closely related to obesity pathogenesis and explored the potential mechanism of their role in obesity. This study provided novel insights into the molecular mechanisms and management of obesity.

Fibroblast growth factor-23 as a biomarker of adverse outcomes in patients with coronary artery disease: a meta-analysis.

BACKGROUND: Fibroblast growth factor-23 (FGF-23) level has been linked the adverse outcomes in patients with coronary artery disease (CAD). The purpose of this meta-analysis was to assess the predictive value of blood FGF-23 levels in CAD patients. METHODS: Two authors comprehensively searched PubMed and Embase until 20 August 2021 to identify studies investigating the association of FGF-23 level with adverse outcomes in CAD patients. Outcomes of interest were major adverse cardiovascular events (MACEs), cardiovascular or all-cause mortality. RESULTS: Eight studies with 16,702 patients with CAD were identified. Pooled results showed that elevated FGF-23 level was associated with a higher risk of MACEs (risk ratio [RR] 1.56; 95% confidence intervals [CI] 1.32-1.84), cardiovascular mortality (RR 1.99; 95% CI 1.38-2.86), and all-cause mortality (RR 1.95; 95% CI 1.67-2.27) after adjusted confounding factors. In addition, per doubling increase in the FGD-23 level was associated with a 24% higher risk of MACEs. Each standard deviation increase in the FGD-23 level conferred a 36% higher risk of cardiovascular mortality. CONCLUSIONS: Elevated blood FGF-23 level is associated with a higher risk of MACEs, cardiovascular or all-cause mortality in patients with CAD, even after adjustment for renal function. Blood FGF-23 level may provide important predictive information in CAD patients.

Long noncoding RNA XIST regulates brown preadipocytes differentiation and combats high-fat diet induced obesity by targeting C/EBPα.

BACKGROUND: Activation of brown adipose tissue (BAT) increases energy expenditure, which makes it an attractive therapeutic strategy for obesity. LncRNAs play an important role in adipocyte differentiation and regulation. Here we assessed the effect of lncRNA XIST on brown preadipocytes differentiation and metabolic regulation. METHODS: XIST expression levels were detected in human perirenal (peri-N) and subcutaneous adipose tissues (sub-Q), brown preadipocytes and 3T3-L1 preadipocytes. XIST overexpression and knockdown experiments were performed in brown preadipocytes. XIST overexpression mouse model was established by plasmid injection through tail vein. RESULTS: In human adipose tissues, XIST expression was significantly higher in female than in male individuals. In vitro, XIST expression was significantly up-regulated during brown adipocyte differentiation. XIST knockdown inhibited differentiation of brown preadipocytes, while overexpression of XIST promotes brown preadipocytes to fully differentiation. RNA Binding Protein Immunoprecipitation (RIP) experiment revealed that XIST could directly bind to C/EBPα. In vivo, XIST overexpression prevents high-fat diet induced obesity and improves metabolic dysorder in male mice. CONCLUSION: Our results suggest that XIST combats obesity through BAT activation at least partly by combination with transcription factor C/EBPα.

[Progress in the studies of prostate biopsy methods].

Prostate cancer (PCa) is one of the most common malignancies in aged males, ranking the second in the incidence of malignant tumors in men. Early diagnosis is essential, as advanced PCa is quite difficult to be managed, especially when it becomes castration-resistant or neuroendocrine PCa. Currently, the diagnosis of PCa is often based on pathology by prostate biopsy. Many recent studies focus on the impact of different biopsy methods on the diagnosis of the malignancy, but no consensus has been reached hitherto. This review summarizes various prostate biopsy methods and their latest studies.

Dual Antiplatelet Therapy Plus Argatroban Prevents Early Neurological Deterioration in Branch Atherosclerosis Disease.

[Figure: see text].

Blocking hsa_circ_0074027 suppressed non-small cell lung cancer chemoresistance via the miR-379-5p/IGF1 axis.

Cancer cell chemoresistance is the primary reason behind cancer treatment failure. Previous reports suggest that circular RNA (circRNA) hsa_circ_0074027 (HC0074027) is a crucial modulator of non-small cell lung cancer (NSCLC) disease progression. Herein, we delineated the underlying mechanism of HC0074027-regulated chemoresistance in NSCLC. We employed quantitative real-time polymerase chain reaction (qRT-PCR) or Elisa in the detection of HC0074027, micoRNA-379-5p (miR-379-5p), and insuline-like growth factor I (IGF1) expressions. Cell survival was evaluated via the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Direct associations among HC0074027, miR-379-5p, and IGF1 were examined via dual-luciferase reporter (DLR) and RNA immunoprecipitation (RIP) assays. Lastly, HC0074027 was incorporated into nude mice to examine its biological activity in vivo. Based on our analysis, HC0074027 levels strongly correlated with NSCLC chemoresistance to docetaxel (DTX), cisplatin (DDP), and paclitaxel (PTX). Alternately, HC0074027 silencing enhanced chemosensitivity in vitro. In vivo, HC0074027 downregulation suppressed tumor expansion and increased cancer cell sensitivity to chemotherapy. We also revealed that HC0074027 physically interacts with miR-379-5p to exert its biological function in vitro. Moreover, IGF1 is a functionally crucial target of miR-379-5p in modulating NSCLC chemoresistance in vitro. Finally, we demonstrated that HC0074027 can indirectly modulate IGF1 levels via sequestering miR-379-5p. We demonstrated that HC0074027 promotes NSCLC chemoresistance via sequestering miR-379-5p activity, and modulating IGF1 expression. Our work highlights the significance of HC0074027 in NSCLC chemoresistance and suggests HC0074027 to be an excellent candidate for targeted NSCLC therapy.

The efficacy and safety of PD-1/PD-L1 immune checkpoint inhibitors in treating advanced urothelial cancer: a meta-analysis of clinical trials.

Survival outcomes in advanced urothelial cancer (UC) are dismal. Over the past years, immunotherapy remains an evolving treatment modality for these patients. This meta-analysis was performed to comprehensively evaluate the efficacy and safety of immune checkpoint inhibitors. For this purpose, 18 clinical trials comprising a total of 3,144 patients were identified from the PubMed database up to September 2020. Overall, the objective response rate (ORR) to PD-1/PD-L1 inhibitors was 0.20 [95% confidence intervals (CI) 0.17-0.23]. Furthermore, the pooled 1-year overall survival (OS) and 1-year progression-free survival (PFS) rates were 0.43 (95% CI 0.33-0.53) and 0.19 (95% CI 0.17-0.21), respectively. The summary rates of any-grade and grade ≥3 adverse events (AEs) were 0.66 (95% CI 0.58-0.74) and 0.13 (95% CI 0.09-0.18), respectively. Among the different subgroups, PD-1/PD-L1 inhibitors elicited a promising ORR in patients with lymph node-only metastasis compared to those with visceral metastasis (0.41 VS. 0.17). Additionally, patients with primary tumor in the lower tract had higher ORR compared to those with primary tumor in the upper tract (0.24 VS. 0.15). Briefly speaking, this immunotherapy protocol showed an encouraging efficacy and acceptable safety profile in the treatment of advanced UC. Moreover, our findings provided potential clinical significance for patients with lymph node-only metastasis or primary tumor in the lower tract. However, these exciting findings need further confirmation.

Dual bronchodilator versus inhaled corticosteroid/long-acting ß2-agonist in patients with chronic obstructive pulmonary disease: A meta-analysis of randomized controlled trials.

BACKGROUND: Long-acting muscarinic antagonist/long-acting ß2-agonist (LAMA/LABA, also known as dual bronchodilator) and inhaled corticosteroid/LABA (ICS/LABA) are the cornerstone of maintenance treatment for stable chronic obstructive pulmonary disease (COPD) patients. We aimed to comprehensively compare the efficacy and safety of the two maintenance treatment in COPD patients. METHODS: We searched the database Embase, Cochrane Library, PubMed, and Clinical Trials.gov systematically (from inception until September 2020). Randomized controlled trials (RCTs) comparing dual bronchodilator with ICS/LABA in the treatment of COPD were included. Efficacy and safety endpoints were pooled as mean differences (MDs) and risk ratios (RRs) with 95% confidence intervals (CIs). This meta-analysis was registered with PROSPERO prospectively # CRD42020203314). RESULTS: Fourteen RCTs including 21,496 patients were included. Dual bronchodilator showed a greater improvement in both trough FEV1 (MD = 0.06 L, 95% CI: 0.04-0.07, P < 0.001) and FVC (FVC: MD = 0.12 L, 95% CI: 0.07-0.16, P < 0.001), and a lower risk of pneumonia (RR = 0.62, 95% CI: 0.53-0.72, P < 0.001) in patients with COPD. There were no significant differences neither in the improvement of exacerbations, symptoms, and quality of life, nor in the incidence of cardiovascular events, serious adverse events, all-cause mortality, and withdrawals due to adverse events of treatment between these two maintenance treatments. CONCLUSIONS: Dual bronchodilator is superior to ICS/LABA in improving lung function and is associated with a lower risk of pneumonia in patients with COPD. There are no significant differences in other efficacy and safety profiles between these two maintenance treatments.

Association between inhaled corticosteroids and upper respiratory tract infection in patients with chronic obstructive pulmonary disease: a meta-analysis of randomized controlled trials.

BACKGROUND: We aimed to assess the association between inhaled corticosteroids (ICSs) and the risk of upper respiratory tract infection (URTI) in patients with chronic obstructive pulmonary disease (COPD). METHODS: PubMed, Embase, Cochrane Library and Clinical Trials.gov were searched from inception to October 2019. Randomized controlled trials (RCTs) of any ICSs vs control for COPD with reporting of URTI as an adverse event were included. The study was registered with PROSPERO prospectively (#CRD42020153134). RESULTS: Seventeen RCTs (20,478 patients) were included. ICSs significantly increased the risk of URTI in COPD patients (RR, 1.13; 95% CI 1.03-1.24; P = 0.01; heterogeneity: I2 = 7%). Futher subgroup analyses suggested that short-term use of ICSs increased the risk of URTI (RR, 1.29; 95% CI 1.06-1.56; P = 0.01; heterogeneity: I2 = 14%) but not for long-term use (RR, 1.08; 95% CI 0.97-1.2; P = 0.14; heterogeneity: I2 = 0%). Short-term use of high-dose fluticasone increased the risk of URTI (RR, 1.33; 95% CI 1.03-1.71; P = 0.03; heterogeneity: I2 = 0%) but not for long-term use (RR, 1.12; 95% CI 0.97-1.29; P = 0.13; heterogeneity: I2 = 50%). Medium-dose (RR, 0.97; 95% CI 0.71-1.32; P = 0.84; heterogeneity: I2 = 0%) and low-dose (RR, 1.39; 95% CI 0.92-2.1; P = 0.12; heterogeneity: I2 = 30%) fluticasone did not increase the risk of URTI regardless of duration. Neither mometasone (RR, 1.05; 95% CI 0.87-1.26; P = 0.61; heterogeneity: I2 = 0%) nor budesonide (RR, 1.08; 95% CI 0.77-1.5; P = 0.67; heterogeneity: I2 = 46%) increased the risk of URTI, regardless of dosage or duration. CONCLUSIONS: Long-term use of ICSs does not increase the risk of URTI in patients with COPD. Short-term use of high-dose fluticasone increases the risk of URTI in patients with COPD, but not mometasone or budesonide.

Inhaled corticosteroids and risk of pneumonia in patients with chronic obstructive pulmonary disease: A meta-analysis of randomized controlled trials.

OBJECTIVE: Inhaled corticosteroids (ICS) are generally used to treat patients with chronic obstructive pulmonary disease (COPD) who suffer from repeated exacerbations. Recently, it was reported that ICS treatment increased the risk of pneumonia in COPD patients. But it is controversial.The objective of this paper is to clarify the associations between ICS treatment and the risk of pneumonia in COPD patients. METHODS: PubMed, Cochrane Library, Clinical Trials.gov, and Embase were searched from February 2019 to June 2019. Randomized clinical trials (RCTs) were incorporatedthat compared ICS with non-ICS treatment on the risk of pneumonia in COPD patients. Meta-analyses were conducted by the Peto and Mantel-Haenszel approaches with corresponding 95% CIs. RESULTS: Twenty-five trials (N = 49,982 subjects) were included. Pooled results demonstrated a significantly increased risk of pneumonia with ICS use in COPD patients (RR, 1.59, 95% CI, 1.33-1.90; I2 = 51%). ICS treatment also increased the risk of severe pneumonia (RR, 2.17, 95% CI, 1.47-3.22; I2 = 29%). The results of subgroup analysis based on doses of ICS were consistent with the above. However, subgroup analyses based on types of ICS revealed that fluticasone therapy was associated with an increased risk of pneumonia but not budesonide. In addition, medium- and low-doses of budesonide treatment also did not increase the risk of pneumonia. CONCLUSIONS: Use of ICS increases the risk of pneumonia in patients with COPD. The above is prominent for fluticasone-containing ICSs but not for budesonide-containing ICSs.

HnRNP-F regulates EMT in bladder cancer by mediating the stabilization of Snail1 mRNA by binding to its 3' UTR.

BACKGROUND: Heterogeneous nuclear ribonucleoprotein F (hnRNP-F) has been implicated in multiple cancers, suggesting its role in tumourigenesis, but the potential oncogenic role and mechanism of hnRNP-F in bladder cancer (BC) remain incompletely understood. METHODS: HnRNP-F was identified by proteomic methods. A correlation of hnRNP-F expression with prognosis was analysed in 103 BC patients. Then, we applied in vitro and in vivo methods to reveal the behaviours of hnRNP-F in BC tumourigenesis. Furthermore, the interaction between hnRNP-F and Snail1 mRNA was examined by RNA immunoprecipitation (RIP), and Snail1 mRNA stability was measured after treatment with actinomycin D. Finally, the binding domain between hnRNP-F and Snail1 mRNA was verified by constructing Snail1 mRNA truncations and mutants. FINDING: HnRNP-F is significantly upregulated in BC tissue, and its increased expression is associated with a poor prognosis in BC patients. HnRNP-F is necessary for tumour growth, inducing epithelial-mesenchymal transition (EMT) and metastasis in BC. The changes in Snail1 expression were positively correlated with hnRNP-F at both the mRNA and protein levels when hnRNP-F was silenced or enhanced, suggesting that Snail1 is likely a downstream target of hnRNP-F that mediates its effects on enhancing invasion, metastasis and EMT in BC. The overexpression of hnRNP-F caused an increase in the stability of Snail1 mRNA. Our RNA chip analysis revealed that hnRNP-F could combine with Snail1 mRNA, and we further demonstrated that hnRNP-F could directly bind to the 3' untranslated region (3' UTR) of Snail1 mRNA to enhance its stability. INTERPRETATION: Our findings suggest that hnRNP-F mediates the stabilization of Snail1 mRNA by binding to its 3' UTR, subsequently regulating EMT.

Patient-specific molecular alterations are associated with metastatic clear cell renal cell cancer progressing under tyrosine kinase inhibitor therapy.

The availability of tyrosine kinase inhibitors (TKI) during the past ten years has led to improved response and overall survival of patients suffering from metastatic clear cell renal cell carcinoma (ccRCC). However, most of these tumors will eventually progress due to resistance evolving under therapy. The objective of this pilot study was to determine whether molecular alterations in ccRCC tissues sampled over the course of the disease might be suggestive of potential therapies. We performed whole exome sequencing of nine samples from four patients in the MORE (Molecular Renal Cancer Evolution) trial. We analyzed the mutational patterns in the tissues at baseline and compared them to those detectable in biopsy samples after progression under TKI therapy. We found limited genetic concordance between primary and secondary tumor sites with private mutations in FLT4, MTOR, ITGA5, SETD2, PBRM1, and BRCA1 on progression. One patient who showed an increased mutational load in the metastasis responded to nivolumab treatment. Our data provide evidence for clonal evolution and diverse pathways leading to acquired TKI resistance of ccRCC. Acquired resistance to TKI in metastatic ccRCC is due to intra-tumor heterogeneity and clonal evolution of resistant subclones. Mutations occurring under progression might be informative for alternative targeted therapies.

Long-term use of inhaled corticosteroids and risk of upper respiratory tract infection in chronic obstructive pulmonary disease: a meta-analysis.

Recent studies have suggested that inhaled corticosteroids (ICS) may be associated with higher risks of tuberculosis and pneumonia in patients with COPD. However, it is not known whether ICS increases the risk of upper respiratory tract infection (URTI). Aim of this study was to explore the relationship between ICS and URTI. Through a comprehensive literature search of PubMed, EMBASE, Cochrane Library, and Google Scholar from inception to March 2016, we identified randomized controlled trials of ICS therapy lasting at least 6 months. A meta-analysis by the Peto approach was also conducted to generate summary estimates comparing ICS with non-ICS treatment on the risk of URTI. A total of 14 studies involving 19,777 subjects were considered in the meta-analysis. Compared with non-ICS treatment, ICS were associated with a significantly increased risk of URTI (Peto OR: 1.16; 95% CI: 1.05-1.29; I2 = 9%; p = .004). Subgroup analyzes were performed for different dose, high-dose ICS was associated with a significantly increased risk of URTI (Peto OR: 1.19; 95% CI: 1.05-1.34; I2 = 0%; p = .005), whereas low-dose ICS showed a non-significant increased risk of URTI (Peto OR: 1.10; 95% CI: 0.91-1.33; I2 = 0%; p = .32). Moreover, fluticasone was observed with an increased risk of URTI but not mometasone; high-dose fluticasone treatment was associated with a significantly higher risk of URTI but not low-dose. These results suggested to us that ICS use may increase the risk of URTI in patients with COPD, but it should be further investigated.

Impact of resection and systemic therapy on the survival of patients with brain metastasis of metastatic renal cell carcinoma.

Patients with brain metastasis (BM) from renal cell carcinoma (RCC) are associated with poor prognosis. Between 1990 and 2015, data of consecutive RCC patients with BM were retrospectively analyzed from a urologic oncologic database. The treatment outcome was evaluated by overall survival (OS), which was defined as interval from initial diagnosis of BM to death or last follow-up. Statistical analyses of clinical and pathological variables were performed using Cox regression and the Kaplan-Meier method. A total of 116 RCC patients with BM were included. Median time from initial diagnosis of RCC to BM was 15.8 months (95 % CI 11.6-20.0). Median OS after diagnosis of brain metastases of the whole cohort was 5.8 months (95 % CI 4.3-7.2). On multivariate Cox regression analysis, age and histology of non-clear cell RCC were associated with poorer outcome, while targeted therapy (n = 26) (OS 9.9 months, 95 % CI 3.3-16.5) and BM resection (n = 33) (OS 24.7 months, 95 % CI 4-40) were associated with better survival. Furthermore, patients who underwent both targeted therapy and BM resection (n = 5) had the best outcome with median OS of 52.4 months. In conclusion, BM from RCC is associated with a poor oncological outcome. Furthermore, age and histology of non-clear cell RCC are risk factors for poor prognosis. Patients with resectable BM may comprise a better prognostic group. Here, a better OS for resected than unresected patients was observed, which warrants BM resection. A combined modality approach of resection and targeted therapy appears to further improve the outcome of these patients while additional radiation seems to add no benefit.

A greater number of dissected lymph nodes is associated with more favorable outcomes in bladder cancer treated by radical cystectomy: a meta-analysis.

The optimal extent of lymph node dissection (LND) is currently not established, and the debate regarding the association between the number of dissected nodes and the outcomes of bladder cancer treated by radical cystectomy (RC) is still ongoing. Therefore, the present meta-analysis was performed to clarify this potential relationship. Eligible studies were retrieved via an electronic search for studies published up to April 2016, and by manual review of the references. A total of 25 cohort studies involving 41,400 bladder cancer patients who underwent RC were included. The summary relative risk estimates (SRRE) based on the highest compared with the lowest categories of LND were estimated by variance-based meta-analysis. Heterogeneity among the study results was explored through stratified analyses. Overall, bladder cancer patients with the highest category of LND had 28%, 34% and 36% reduced risks, corresponding to overall survival (SRRE = 0.72; 95% CI, 0.64-0.80), cancer-specific survival (SRRE = 0.66; 95% CI, 0.54-0.80) and recurrence-free survival (SRRE = 0.64; 95% CI, 0.50-0.82), respectively, compared with patients with the lowest category of LND. In summary, the patients with a greater number of dissected lymph nodes had statistically significant survival advantages in terms of the outcomes of bladder cancer following RC. The number of dissected lymph nodes could be an independent prognostic factor for bladder cancer. These findings need to be validated in prospective and larger epidemiological studies with a longer follow-up period.

Survival and prognostic factors of patients with renal cell cancer with bone metastasis in the era of targeted therapy: A single-institution analysis.

OBJECTIVE: To analyze the survival and prognostic factors of patients with renal cell carcinoma (RCC) with bone metastasis (BM). METHODS AND MATERIALS: Data of all patients with RCC with BM treated between January 2006 and March 2015 were retrieved from our database and analyzed retrospectively. Overall survival (OS) from diagnosis of BM was analyzed for the whole cohort and selected subgroups. Statistical analyses of clinical and pathological variables were performed using Cox regression and the Kaplan-Meier method. RESULTS: A total of 114 patients were included. Median time from initial diagnosis of RCC to BM was 5.5 months (95% CI: 2.7-8.3). Median OS of the whole cohort was 9.6 months (95% CI: 5.5-13.6). On multivariate Cox regression analysis, targeted therapy (TT), resection of BM, and bisphosphonate treatment were favorable factors for the OS, whereas sarcomatoid features and high Fuhrman grade were unfavorable factors for OS. The median OS of 78 patients with TT was 9.9 months. Resection of BM in combination with TT (n = 24) resulted in a superior OS of 31.8 months (95% CI: 16.0-47.6) compared with TT only (n = 40) with an OS of 7.6 months (95% CI: 5.8-9.3). CONCLUSIONS: Resection of BM in combination with TT significantly improves the survival of patients with RCC with BM over TT only. Sarcomatoid features and G3/G4 Fuhrman grade are independent factors of poor prognosis.

The increased excretion of urinary orosomucoid 1 as a useful biomarker for bladder cancer.

Improving the early detection rate and prediction of bladder cancer remains a great challenge in management of this disease. To examine the value of urinary orosomucoid 1 (ORM1) for the early detection and surveillance of bladder cancer, two-dimensional differential gel electrophoresis (2-DE) and matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF/TOFMS) were applied to identify the differently expressed proteins in urine between bladder cancer and healthy controls. Thirteen different proteins including ORM1 were identified. After verification by western blotting, the ORM1 expressions were quantified in 186 urine samples by enzyme-linked immunosorbent assay (ELISA) correcting for creatinine expression. ELISA quantification showed the urinary ORM1-Cr was found to be higher in bladder cancer patients compared to controls and benign cases (7172.23±3049.67 versus 2243.16±969.01, 2493.48±830.37 ng/ml, respectively, P<0.0001). Furthermore, the pearson correlation analysis indicated that urinary ORM1 had high positive correlation with the pathology classification of bladder cancer. Receiver operating characteristic (ROC) analysis was used to calculate the cut-off value for early diagnosis of bladder cancer, and rendered an optimum cut-off value of 3912.97 ng/mg corresponding to 91.96% sensitivity and 94.34% specificity. Moreover, a cut-off value with 7351.28 ng/mg was utilized to distinguish infiltrating urothelial carcinoma from bladder cancer patients corresponding to 91.89% sensitivity and 90.67% specificity. In conclusion, our findings suggested the elevated urinary ORM1 could be a useful biomarker for bladder cancer. Further research is warranted to elucidate the pathogenic mechanisms of elevated ORM1.

Local Recurrence After Curative Surgical Treatment of Renal Cell Cancer: A Study of 91 Patients.

BACKGROUND: Local recurrence (LR) after curative therapy for renal cell cancer is a rare event, and surgery is still the primary treatment option. PATIENTS AND METHODS: This was a single-institution, single-arm retrospective study from a prospectively conducted database. A total of 91 patients with a median age of 63.0 years (interquartile range, 57.5-68.3), who had undergone LR resection after initial curative treatment of RCC were enrolled. The time to LR (TTLR) was defined as the interval from primary curative surgery to LR. Cancer-specific survival, overall survival, and progression-free survival were evaluated after LR resection. Statistical analyses of the clinical and pathologic variables were performed using Cox regression analysis and the Kaplan-Meier method. RESULTS: The median time to LR was 29.8 months (interquartile range, 10.8-64.3). On multivariate analysis, age > 65 years, T3/T4 stage, Fuhrman grade 3/4, major venous infiltration, and positive surgical margins were related to early LR after primary curative surgery. LR size of ≤ 7 cm and TTLR of > 24 months were associated with longer cancer-specific survival. Furthermore, patients with a TTLR of > 24 months had better overall survival and progression-free survival. Of the entire cohort, intraoperative radiation therapy and targeted therapy were used in 17 (18.7%) and 15 (16.5%) patients, respectively. CONCLUSION: Advanced age, T3/T4 stage, Fuhrman grade 3 or 4, major venous infiltration, and positive surgical margins at primary tumor resection were related to a greater risk of early LR. An LR size of ≤ 7 cm and TTLR of > 24 months were associated with favorable oncologic outcomes after LR resection. Thus, patients who present with a longer TTLR and smaller LR size, along with favorable features at primary tumor resection, will benefit from surgical treatment.

Functional Effects of WNT1-Inducible Signaling Pathway Protein-1 on Bronchial Smooth Muscle Cell Migration and Proliferation in OVA-Induced Airway Remodeling.

Upregulation of WISP1 has been demonstrated in lung remodeling. Moreover, it has been recently found that some signaling components of WNT pathway can activate GSK3ß signaling to mediate remodeling of airway smooth muscle (ASM) in asthma. Therefore, we hypothesized that WISP1, a signaling molecule downstream of the WNT signaling pathway, is involved in PI3K/GSK3ß signaling to mediate ASM remodeling in asthma. Our results showed that WISP1 depletion partly suppressed OVA-induced ASM hypertrophy in vivo. In vitro, WISP1 could induce hBSMC hypertrophy and proliferation, accompanied by upregulation of levels of PI3K, p-Akt, p-GSK3ß, and its own expression. TGF-ß treatment could increase expression of PI3K, p-Akt, p-GSK3ß, and WISP1. SH-5 treatment could partly suppress TGF-ß-induced hypertrophy and proliferation of hBSMC, and depress expression of p-GSK3ß and WISP1. In conclusion, WISP1 may be a potential inducer of ASM proliferation and hypertrophy in asthma. The pro-remodeling effect of WISP1 is likely due to be involved in PI3K-GSK3ß-dependent noncanonical TGF-ß signaling.